The present invention relates to chromatography systems, and more particularly the use of automation technology in the qualification of chromatography systems.
Chromatography systems are used to analyze various products developed by pharmaceutical companies, hospitals, and government laboratories. Such products in many cases are regulated by the United States Food and Drug Administration (the xe2x80x9cFDAxe2x80x9d) and other foreign regulatory agencies, therefore regulatory guidelines require the validation of these chromatography systems for laboratories submitting data, e.g. pharmaceutical samples to the above regulatory agencies. The regulatory requirements demand that the chromatography systems that are used to analyze products must meet certain minimum requirements as many regulatory agencies will not accept data from laboratories that have not established that they are using validated chromatography systems.
When a chromatography system satisfies the validation requirements, it is said to be xe2x80x9cqualifiedxe2x80x9d. A qualified chromatography system generally must meet the articulated standards in three separate areas. The three areas are installation, operation, and performance. Each area is described below.
The installation qualification (xe2x80x9cIQxe2x80x9d) verifies that the chromatography system satisfies three conditions associated with the installation of the system. First, the IQ establishes the chromatography system is received as designed. Second, it verifies the chromatography system is installed properly. Lastly, the IQ verifies that the environment where the system is installed is appropriate.
The operational qualification (xe2x80x9cOQxe2x80x9d) ensures the instruments which comprise the chromatography system function according to their individual operational specifications in the chosen environment. An OQ does not specifically verify that individual modules successfully perform as part of an integrated system.
The performance qualification (xe2x80x9cPQxe2x80x9d) ensures the integrated chromatography system routinely performs according to specification.
Conventional methods for qualifying chromatography systems include manuals, qualification workbooks, and metrology based qualifications. An example is the Waters HPLC Systems Qualification Workbook developed by Waters Corporation of Milford, Massachusetts. This highly manual and labor intensive process takes from 10-12 hours to finish per chromatographic system. Qualification via qualification workbooks is extremely time consuming because the individual modules and the integrated system are qualified separately.
Attempts to automate the qualification systems, such as with the Hewlett Packard 1100, have not been successful. The HP method is merely a manual system with the only improvement being that the workbook for the use of the system is contained on a cd-rom.
Another disadvantage of conventional methods of qualification is that different samples, solvents, and methods are used in the qualification of the modules (OQ) and those used for the qualification of the system (PQ). are different than those used by the lab on a daily basis. Consequently, a significant amount of time is lost in removing solvents and samples from the chromatograph and documenting the multiple reagents and samples used in system qualification. Therefore, conventional methods take too much time and require constant technical human intervention. Because of the demands of continual human intervention, the cost to industry is excessive. Additionally, the need to maintain and retrieve the various qualification reports is burdensome and not amenable to the advantages of electronic format.
The present invention provides methods and apparatus for automating the qualification process for chromatographic systems.
According to the invention automation technology and regression analysis are used for qualifying a chromatography system. In order to practice the present invention, certain steps must be performed. The initial step involves preparing the chromatography system to ensure that the samples, solvents, and the separation column are ready for analysis. After the chromatography system has been prepared, automated steps are performed to qualify the detector, the solvent delivery system, the sample manager, the gradient proportioning system, the column heater, and the delay volume of the chromatography system. Regression analysis is performed to compute performance statistics that demonstrate the accuracy, linearity, and precision of the chromatographic system and quantify its suitability for chromatographic analysis.
In an illustrative embodiment, the automated qualification systems application is built using the Millennium32 vV3.20 Toolkit Option (Professional Edition, Waters Corporation) and Microsoft Visual Basic 6.0 (Enterprise Edition, Microsoft Corporation).
Advantages of the invention include the use of automation technology to provide a substantially faster way to qualify chromatography systems. Less time is required for qualification, thus the cost of qualification is lowered enabling more frequent qualifications. The method according to the invention minimizes contamination of the chromatography systems with solutions which are not suitable as mobile phases that could interfere with normal operation in subsequent analyses. The testing is based on xe2x80x9cnormal/intendedxe2x80x9d use of chromatograph and data system, which is consistent with the current FDA regulations and does not use procedures and materials substantially different from the primary application. Further, the operator, after initial procedures are performed, is allowed to utilize their time attending to other matters, as the invention requires no additional human intervention during the qualification process. The production of various reports in an electronic format allows off site review and the generation of varied format reports. Test results can be archived in an efficient electronic format.